1. Field of the Invention
This invention pertains generally to load-induced muscle growth and strength training and more particularly to methods for improving muscle hypertrophy in mammals by inhibiting sirtuins in muscles in combination with other muscle growth approaches.
2. Description of Related Art
Skeletal muscle is a very adaptive tissue and muscle mass in the body is regulated by nutritional, hormonal and mechanical cues. Muscular strength is directly linked to health, such that the mortality rate of individuals with low muscle strength is twice that of a high strength counterpart. Functionally, low muscle strength limits mobility, independence, and recovery from surgery and metabolically low muscle mass increases the risk of diseases such as diabetes. Therefore, increasing muscle mass and strength has important implications on the health, longevity, and quality of life of people.
Generally, muscle hypertrophy, or the enlargement of muscle fibers, is a process that includes load-induced changes in transcription and translation in the cells through a number of pathways. For example, the IGF-1 signaling pathway is a well-known cascade contributing to the development of skeletal muscle hypertrophy.
Increased activity of the mechanistic target of rapamycin (mTOR) correlates with and is required for skeletal muscle growth. Factors associated with reduced cellular energy status have been proposed to suppress mTOR signaling and thereby limit skeletal muscle hypertrophy. However, whether this effect is mediated exclusively by the metabolic stress proteins described to date has yet to be demonstrated.
The NAD+-dependent protein deacetylase, sirtuin1 (SIRT1), is another candidate for integrating and transducing changes in cellular energy flux to the muscle and preventing growth. SIRT1 activity is increased by metabolic stress such as seen during calorie restriction or endurance exercise. Both caloric restriction and endurance exercise are known to blunt muscle growth, suggesting that SIRT1 might inhibit muscle protein synthesis and the hypertrophic response to loading.
Accordingly, there is need for preparations and methods that will help reverse age related muscle atrophy or allow for accelerated skeletal muscle growth from weight training. The present invention satisfies these needs as well as others and is an improvement in the art.